The dorsal sensory neuron conveys visceral and somatic sensory information to the spinal cord and dorsal medulla. These data are important in the perception of tactile sensation, pain, and in the control of autonomic functions, posture, movement and fine motor function. Sensory information is imparted to central neurons by chemically mediated synaptic transmission. Identifying the transmitters involved and understanding their biochemistry is of practical use as insights would be provided into the means to modulate sensory input. Such control could be valuable to help re-establish autonomic functions and suppress excessive spastic movements in spinal trauma, to help modulate motor function impaired by diseases of the CNS, and to help suppress pain with nonaddictive compounds. Glutamate (GLU) and substance P were proposed as the transmitters in the dorsal sensory axons. In fibers carrying modalities other than pain, GLU is presumed to be the transmitter because in areas where they synapse, GLU levels are relatively high and GLU strongly excites neurons. As evidence is lacking that GLU is actually contained in and released from primary afferents, its transmitter role in these fibers is uncertain. The proposed research is designed to test the hypothesis of a transmitter role for GLU in primary afferents; a combination of neurochemical, surgical, and histological techniques will be used to assess if GLU is contained in and released by primary afferent endings in the spinal cord and dorsal column nuclei, mainly of guinea pigs, but also of rats and cats. The specific goals are: (A) To establish whether primary afferents, descending fibers, or intrinsic neurons contain high concentrations of GLU: the destruction of these elements by dorsal rhizotomy, spinal hemisection, and kainic acid will be monitored histologically while GLU and other compounds will be measured in microdissected tissue fragments. (B) To determine if the tissue elements listed above release GLU during impulse transmission from primary afferents; using the above lesions, release of GLU and other compounds will be measured in vivo and in vitro. (C) If GLU is released from primary afferents, to assess if the mechansim of release is compatible with its proposed transmitter role.